Dysautonomia Foundation, Inc.

Overview:
In individuals with FD, a progressive neurogenetic disorder, the
autonomic and sensory nervous systems malfunction. Symptoms vary,
and may include insensitivity to pain, unstable blood pressure and
body temperature, absence of overflow tears, frequent pneumonia, and
poor growth. FD is often associated with a shortened lifespan.
Individuals with FD suffer from episodes of cyclical vomiting
accompanied by extremely high blood pressure and increased heart rate,
sweating and fever. These �autonomic crises� are one of the most
devastating symptoms of this disease, often requiring
hospitalization.

Name of disease: familial dysautonomia (FD), also known as
Riley-Day Syndrome
Carrier frequency in Ashkenazi Jews: 1 in 27
Carrier frequency in the general population: unknown
Age of onset: birth

Symptoms: FD causes dysfunction of the autonomic and sensory
nervous systems. It is a progressive disease. Symptoms and severity
vary in each patient. Symptoms include:

Absence of overflow tears / corneal drying

Poor suck at birth

Drooling

Swallowing & feeding problems

Hypotonia / poor muscle tone

Short stature

Delayed developmental milestones: motor, language,
social

Inappropriate temperature controls

Wide swings in blood pressure

Gastro-esophageal reflux

Frequent lung infections or pneumonias

Episodic vomiting

Decreased or no
reaction to pain and temperature

Excessive sweating

Blotchy reddening of
skin with excitement and/or feeding

Smooth tongue / lack
of taste buds

Spinal curvature

Poor weight gain and
growth

Impaired renal
function

Osteoporosis and
osteopenia

Fainting and cardiac
arrhythmias

Sleep apnea

Restrictive lung
disease

Average lifespan: Currently, the mean age of the FD
population is approximately 15 years. By statistical projection,
babies born with FD in 2006 have a 50% chance of surviving to 40
years of age. The major causes of death are the result of pulmonary
complications or sudden death due to autonomic instability.

What is the basis of disease: Inefficient gene splicing
results in decreased production of a vital protein called IKAP. This
protein is an essential component of a complex that aids in
expression of multiple other target genes that are critical for
growth and development of the sensory and autonomic nervous systems
as well as their function.

Treatment or management:There is no cure for
FD. Treatments are supportive and preventative. Supportive therapies
include medications to maintain and regulate cardiovascular,
respiratory, and gastrointestinal function. Surgical interventions
include fundoplication, gastrostomy, spinal fusion, and tear duct
cautery.
Various therapies are used to promote
strength and speech development.

Carrier testing: Carrier testing is available for the two
most common mutations. All patients have one or two
copies of a single splicing mutation; over 99% of cases of FD in the
Ashkenazi Jewish (AJ) population have two copies of this splicing
mutation. A second mutation paired with the AJ splicing mutation
accounts for all other cases in the AJ population. A third mutation
from a non-Jewish parent, again paired with the AJ splicing
mutation, is responsible for a single case of FD.

Other testing information: Carrier
screening is based on DNA analysis. Screening is 99% accurate for
the AJ population.

Current research: Research focuses on modifying the splicing
defect in order to increase production of IKAP as well as to further
understand the role of this vital protein. Researchers are also
constructing an FD mouse model to further this aim. Clinical
investigations include assessment of sleep physiology and assessment
of molecular and functional biomarkers.